title: Inhibition by valproic acid of pyruvate uptake by brain mitochondria.
abstract: The anticonvulsive drug, valproic acid, inhibits competitively the pyruvate carrier in rat brain and liver mitochondria. Due to this inhibition the oxygen consumption supported by pyruvate oxidation is also affected. In our experimental conditions, pyruvate oxidation is partially inhibited by VPA concentration as low as 0.05 mM. Valproic acid, however, is unable, even at 10 mM, to fully inhibit pyruvate oxidation. Concentrations of VPA higher than 1 mM have an uncoupling effect on mitochondrial respiration. The oxidation of other mitochondrial substrates such as isocitrate, 2-ketoglutarate, DL-3-hydroxybutyrate and succinate is uncoupled but not inhibited by VPA. The effects of VPA on mitochondrial metabolism may be related to the therapeutic and/or toxicologic properties of this drug.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D011773:Pyruvates; D014635:Valproic Acid; D019289:Pyruvic Acid